CA125 gene and its use for diagnostic and therapeutic interventions

Abstract

The CA125 gene has been cloned and multiple repeat sequences as well as the carboxy terminus have been identified. The CA125 molecule comprises three major domains: an extracellular amino terminal domain (Domain 1); a large multiple repeat domain (Domain 2); and a carboxy terminal domain (Domain 3) which includes a transmembrane anchor with a short cytoplasmic domain. The amino terminal domain is dominated by its capacity for O-glycosylation and its resultant richness in serine and threonine residues. An amino terminal extension is presented, which comprises four genomic exons. The molecular structure is dominated by a repeat domain comprising 156 amino acid repeat units, which encompass the epitope binding sites. More than 60 repeat units have been identified, sequenced, and contiguously placed in the CA125 domain structure. More specifically, this invention is directed to a CA125 cDNA sequence which can be introduced into animal or human cells to achieve transcription or expression of the cDNA.

We claim: 
     
       1. An isolated nucleic acid molecule encoding residues 10,432 to 22,152 of SEQ ID NO:5 or a fragment of residues 10,432 to 22,152 of SEQ ID NO:5;
 wherein the isolated nucleic acid molecule is an expression vector and is adapted to express in a cell residues 10,432 to 22,152 of SEQ ID NO:5 or a fragment of residues 10,432 to 22,152 of SEQ ID NO:5; 
 wherein the fragment of residues 10,432 to 22,152 of SEQ ID NO:5 is: 
 (a) a fragment of residues 12,070-22,152 of SEQ ID NO:5 at least 300 consecutive residues in length and comprising an antigenic fragment of one or more sequences selected from the group consisting of: 
 residues 12128-12148, 12284-12304, 12384-12539, 12540-12694, 12695-12850, 12851-13006, 13537-13630, 13689-13709, 13845-13865, 14001-14021, 14157-14177, 14313-14333, 14469-14489, 14627-14647, 14783-14803, 14939-14959, 15037-15192, 15193-15348, 15349-15504, 15505-15659, 15650-15815, 15816-15971, 16030-16050, 16127-16282, 16341-16361, 16497-16517, 16595-16750, 16751-16906, 16907-17062, 17121-17141, 17219-17374, 17375-17530, 17589-17609, 17687-17842, 17901-17921, 18057-18077, 18213-18233, 18369-18389, 18525-18545, 18623-18778, 18837-18857, 18993-19013, 19149-19169, 19305-19325, 19461-19481, 19560-19714, 19773-19793, 19870-20025, 20084-20104, 20240-20260, 20338-20493, and 20806-20961 of SEQ ID NO:5; or is 
 (b) an antigenic fragment of residues 10,432-22,152 of SEQ ID NO:5 at least 150 consecutive residues in length and comprising an antigenic fragment of either residues 10,432-10563 or residues 11219-12069-of SEQ ID NO:5. 
 
     
     
       2. The isolated nucleic acid of  claim 1  wherein the fragment of residues 10,432-22,152 is an antigenic fragment of residues 10,432-22,152 of SEQ ID NO:5 at least 150 consecutive residues in length and comprising an antigenic fragment of either residues 10,432-10563 or residues 11219-12069-of SEQ ID NO:5. 
     
     
       3. The isolated nucleic acid of  claim 1  wherein the fragment of residues 10,432-22,152 is a fragment of residues 12,070-22,152 of SEQ ID NO:5 at least 300 consecutive residues in length and comprising an antigenic fragment of one or more sequences selected from the group consisting of:
 (a) residues 12128-12148, 12284-12304, 12384-12539, 12540-12694, 12695-12850, 12851-13006, 13537-13630, 13689-13709, 13845-13865, 14001-14021, 14157-14177, 14313-14333, 14469-14489, 14627-14647, 14783-14803, 14939-14959, 15037-15192, 15193-15348, 15349-15504, 15505-15659, 15650-15815, 15816-15971, 16030-16050, 16127-16282, 16341-16361, 16497-16517, 16595-16750, 16751-16906, 16907-17062, 17121-17141, 17219-17374, 17375-17530, 17589-17609, 17687-17842, 17901-17921, 18057-18077, 18213-18233, 18369-18389, 18525-18545, 18623-18778, 18837-18857, 18993-19013, 19149-19169, 19305-19325, 19461-19481, 19560-19714, 19773-19793, 19870-20025, 20084-20104, 20240-20260, 20338-20493, and 20806-20961 of SEQ ID NO:5. 
 
     
     
       4. The isolated nucleic acid molecule of  claim 3  wherein the fragment of residues 10,432-22,152 of SEQ ID NO:5 is a fragment of residues 12,070-22,152 of SEQ ID NO:5 at least 450 consecutive residues in length. 
     
     
       5. The isolated nucleic acid molecule of  claim 3  wherein the fragment of residues 10,432-22,152 of SEQ ID NO:5 is a fragment of residues 12,070-21,720 of SEQ ID NO:5 at least 300 consecutive residues in length. 
     
     
       6. An isolated nucleic acid molecule encoding CA125 (SEQ ID NO:5) or a fragment thereof;
 wherein the isolated nucleic acid molecule is an expression vector and is adapted to express in a cell CA125 (SEQ ID NO:5) or a fragment thereof; 
 wherein the fragment thereof is an antigenic fragment of a sequence selected from the group consisting of residues 1-563, 654-1317, 1803-2095, 3846-6980, 7053-7531, and 7629-8408 of SEQ ID NO:5. 
 
     
     
       7. The isolated nucleic acid of  claim 6  wherein the fragment thereof is an antigenic fragment of residues 312-399 of SEQ ID NO:5.